Why is exercise good for us

 
Exercise has enormous benefits for those with cancer

Most of us realise that regular exercise and a healthy lifestyle reduces our risks of developing cancer,  whether we do something about it or not. What is less well known are the enormous benefits of exercise after a diagnosis of cancer. It improves  well-being and exercise increases the chances of cure (Table.1).  In many cases the magnitude of these benefits is on a par with that provided by chemotherapy, yet mainstream oncology units have been slow to offer exercise guidance and support for their patients.

This article analyses the evidence from established clinical studies, describes the underlying mechanism of how exercise fights cancer and proposes a system which would integrate exercise and lifestyle rehabilitation into routine clinical management. It is only through research that we can ensure that proper advice is given to the correct people at the appropriate time in their pathway. It is also necessary to persuade health care providers to allocate sufficient funds and resources (by Professor Robert Thomas FRCP MD FRCR and Cecilia Nicholson, Patient and Journalist).

Exercise to help prevent cancer

A recent British overview of several published studies showed that a lifestyle which includes regular exercise could prevent 14% of male and 20% of female cancer deaths in the UK alone.  For colorectal cancer specifically, another UK study demonstrated that the difference between those at the highest levels of physical activity compared to the lower levels, is up to 40%. The latest analysis from Washington, USA, which combined all available studies published for bowel cancer up to March 2009, gave an average reduction figure of 24%. This percentage benefit implies that increasing physical activity may be the most important risk factor that is amenable to modification by individuals wishing to reduce their risk of this cancer.

Exercise to reduce the risks and side effects during cancer treatments

Although the common side effects of fatigue, nausea and pain are considerable motivational barriers to exercise during cancer therapies, there is now compelling evidence that it is worth the extra effort to put on a pair of sturdy shoes, brave the unpredictability of our British weather and go for a brisk walk or jog. Here are some of the symptoms that can be improved by regular light exercise which have been confirmed by well conducted clinical studies.

Fatigue and tiredness:  A comprehensive study from Philadelphia, USA suggest this to be a significant problem for between 65-90% of patients receiving chemotherapy. For some, the fatigue was strong enough to influence nutritional status and negatively affect chemotherapy dose intensity. Interestingly, in the same study, doctors believed fatigue only affected 30% of their patients, a significant disparity between medical perception and the reality. Fortunately a number of other studies have demonstrated that, as well as correcting haemoglobin and providing sleep hygiene guidance, regular light exercise can improve fatigue and quality of life issues for patients with cancer, particularly those on chemotherapy.

Blood clots (Thromboemolism) remain a significant risk for patients with malignancy, particularly those affecting the pelvis, recent surgery or immobility, a previous history of blood clots or those receiving chemotherapy. Although strategies such as compression stockings, warfarin and heparin are essential, exercise has been shown to be of  major benefit in reducing this life threatening complication.

Body composition, particularly weight gain during and after adjuvant chemotherapy, is becoming an ever increasing concern. Women with breast cancer, for example, report a 45% incidence of significant weight gain often at a time in their lives that makes losing it difficult. There are several reasons for this; some patients concerned about weight loss, perhaps from dated and misleading information sources, tend to over-eat; others, experiencing fatigue and nausea, stop exercising. Drugs, including steroids and hormone therapies such as tamoxifen, are also exacerbatory factors. Whatever the cause, numerous exercise intervention studies have demonstrated significant improvement in body fat, lean mass indices, bone mineral density, muscle strength, joint pains and walking distance.

Mood, depression, anxiety and panic disorders are commonly under-diagnosed for patients with cancer. A recent survey reported these to be present in up to 50% individuals for several months after their diagnosis. These episodes might be triggered by medical appointments, newspaper articles and other reminders. Not only is this distressing for patients and their carers, studies have suggested that depressed patients with lung and breast cancer have a reduced survival rate than those who are psychologically healthy. Fortunately, a number of prospective exercise intervention studies among patients receiving therapies ranging from chemotherapy, radiotherapy and hormone therapies, have demonstrated reduced levels of depression, anxiety and improved mood and quality of life. Furthermore, exercise after a diagnosis of cancer enhances the degree of self empowerment, both from the patients and carers who can also join in with the activity. It is well known that patients who feel empowered with their own management process are known to be more satisfied and have better psychological adjustment to their illness.

Constipation caused by immobility, painkillers opiate or anti sickness drugs during chemotherapy, remain a significant patient concern. Exercise in addition to dietary changes reduces bowel transit time and ameliorate constipation and its associated abdominal cramps. 

Exercise to slow the rate of established cancer progression

Most of the reliable evidence for the effect of lifestyle on cancer progression comes from trials which involve patients with non-aggressive or relapsing prostate cancer. The slow growth rate in many patients and availability of a simple blood test (PSA) allows time for alternative interventions, making them acceptable to both clinician and motivated patients alike.

The first category of evidence comes from studies that looked back at patients diet and lifestyle with questionnaires and interviews. These studies, known as retrospective studies, established that patients who previously had higher levels of exercise and healthy diet had less aggressive, less advanced disease at presentation associated with a much better prognosis. They also showed that patients who improved their lifestyle after diagnosis, compared with those renowned for a couch potato attitude, were less likely to transformation from early prostate cancer into a more advanced stage.

More persuasive evidence comes from trials designed to look forward, following a lifestyle intervention. These trials, called prospective studies, have predetermined, robust endpoints, which are recorded in designated trial documentation at regular intervals. It is not possible after the trial has begun, unlike retrospective studies, to change the specified endpoints. This makes the conclusions of these trials generally more reliable and convincing. Fortunately, there are two prospective studies in men with prostate cancer which, deservedly, generated copious media attention at their time of publication.

The first study involved 93 volunteers from the USA with early prostate cancer who, for various reasons, had declined undergoing conventional therapies. They were randomly assigned to intensive nutritional and exercise counselling, or simple active surveillance. In the 47 patients randomly assigned to lifestyle, they changed to a high vegetable and fruit diet supplemented with soy, vitamin E, fish oils, selenium and vitamin C. Physiotherapist also guided them into a moderate exercise program requiring at least thirty minutes of walking six days a week. The PSA decreased at twelve months in the intervention group by 4%, but increased in the control group by 6%. When this difference was analysed independently by scientific statisticians, it was shown to be highly significant. In other words it was a difference which was very unlikely to have occurred by chance (greater than 1:50 odds). Put another way everyone believed it!

The trial had another intriguing twist. A blood sample was taken from all patients at three monthly intervals. After removing the blood cells, the serum was added to sheets of living prostate cancer cells grown in culture dishes in a laboratory. Serum from the intervention group caused 70% of the laboratory prostate cells to stop growing, whereas serum from the control (non intervention group) only inhibited growth in 6% of cells. This eight-fold difference (70% v 6%) was highly significant and again statistically robust (fewer than 1:100 odds that it happened by chance).
 
The research unit at Bedford, Cranfield University and Addenbrookes Hospital conducted a double-blind, randomised, multi-centre controlled trial under the registration of the National Cancer Research Network. As part of its design the study looked at the rate of PSA progression before and after a lifestyle intervention which included exercise guidance and counselling. The result, published in early 2009, showed that despite the fact that all patients were progressing at trial entry, 40% then stabilised for an average of 18 months.

These trials convincingly demonstrate that lifestyle, including exercise, can alter the rate of cancer progress but it must be remembered that at the present time the evidence is restricted to non-aggressive prostate cancers and these patients were also carefully supervised within an active surveillance program. We must be careful not to extrapolate this data to other cancer types without further thorough investigation. It must also be noted that a lifestyle intervention did not help everyone, despite the best will in the world, so patients should not feel to blame if these interventions were not effective in their particular case.

Evidence that exercise can help to prevent cancer relapse

A number of studies have proven that patients who exercise regularly after their initial cancer treatments have a lower risk of their cancer returning and live longer. The two most convincing studies involved men and women with bowel cancer. The first involved 526 patients, recruited between 1990 and 1994 from the Melbourne Collaborative Cohort Study in Australia. At trial entry, shortly after their diagnosis, body fat measurements were taken and patients were interviewed about their physical activity over the prior six months. The body mass index was calculated from the weight, height and waist to hip ratio measurement. Patients were defined as exercisers or non-exercisers. Exercisers were classified as those taking recreational activities or sports two or more times per week that made them sweat or feel out of breath,. Body composition was also measured by bioelectrical impedance using a single frequency electrical current. A comparison was made of the numbers of patients in the two groups who relapsed or died over the next five years. The results showed that, taking into account the standard risk factors, 57% of patients were alive at five years in the non-exerciser group, and 71% in the exerciser group. This 14% difference was statistically highly significant. As regards death, specifically from bowel cancer, there was a 12% difference (61% v 73%). Again, very significant.

A similar finding was indicated in an American study involving 816 patients with cancer of the colon. All patients had a disease that was completely removed, but also had evidence of spreading to the local lymph nodes (stage III). They completed detailed lifestyle questionnaires during and after additional chemotherapy that generally lasted for six months. Increased physical activity was associated with a lower chance of the disease relapsing and an improved overall survival. In practical terms this equated to a 35% difference in relapse rate for individuals in the highest quintile of regular physical activity, compared with the lowest quintile. To put this in perspective, if a pharmaceutical company invented a drug to achieve this degree of benefit it would be on the front page of every newspaper and the public would be rioting in the streets to get hold of it!

How does exercise fight cancer?

There are five accepted underlying mechanisms showing how exercise has cancer fighting properties:

Weight reduction:  Although seemingly obvious, the observation that exercise helps to reduce weight among patients with cancer is supported by a large USA study, which reported a significant decrease in body fat after physical exercise counselling. Obesity is harmful because it increases the levels of circulating oestrogen and testosterone, two hormones linked to breast, uterine and prostate cancers. Even with medication to suppress oestrogen production, some oestrogen is stored in fat cells. Exercise helps by converting fat to muscle.

Blood fat levels: Regular exercise has been shown to help control the bodys levels of blood lipids and cholesterol independent of body weight. High serum fat levels have been particularly associated with a greater risk of a more advanced and aggressive type of cancer, with a higher possibility of relapse after initial therapy. Men with prostate cancer, with lower serum lipids, have better prognostic features including lower PSA, lower aggressiveness of cells (grade) and less advanced stage of the cancer. These factors correlate with better outcomes. A clue to the mechanism of fat levels, at least in prostate cancer, comes from the finding that lower serum fat levels correlated with lower testosterone.  

Decreasing bowel transit time:  Exercise decreases the time it takes for waste to pass through the bowel. Stagnant stools in the colon are thought to increase the risk of cancer by exposing the carcinogens that have not been absorbed in our diet to the mucous membrane of the bowel lining for longer. Patients who have developed one bowel cancer are more likely to develop a second. Reducing the carcinogen exposure time to the gut is likely, therefore, to be even more helpful in this higher risk group. 

Immune pathway: An important component of immunity and healing involves the production of prostaglandins in the body. These are biologically active fats generated via the enzyme cycloxidase (COX). The COX-1 subtype is activated in response to trauma, infective or chemical injury, producing prostaglandins that contribute to the inflammatory response we are all familiar with following a wasp sting or healing from a skin cut, for example, leading to redness, swelling and pain. Unfortunately the prostaglandin pathways have also been hijacked by cancers. Those produced by the COX-2 subtype have been shown very sinister implications in the fundamental processes of cancer progression and spread. This includes aiding the formation of new cancer blood vessel (angiogenesis), encouraging cells to grow faster (proliferation), stopping cells from dying when they should (apoptosis) and encouraging them to lose their stickiness to the primary site, so they are more likely to invade other organs and spread elsewhere (metastasis). Obviously, scientists are endeavouring to develop drugs to block the COX-2 enzyme. It is our good fortune that exercise, as well as aspirin-like proteins found in fruit and vegetables, have been shown to inhibit COX-2 production providing one important mechanism of their direct anti-cancer benefit.

The insulin-like growth factor axis: Emerging, yet compelling, evidence supports the idea that physical activity also exerts its beneficial effect on cancer via a protein called insulin-like growth factor (IGF) axis. A number of substantial studies involving patients with established cancer (particularly those with bowel cancer) have shown higher blood levels of insulin-like growth factor 1 (IGF-1). Early studies suggest that after binding to its receptors, which are found on normal colonic mucosal cells as well as colon cancer cells, IGF-1 can stimulate cells to grow faster and in an uncontrolled way, as well as trigger the same fundamental cancer processes mentioned above. People who exercise regularly have been shown to have a convincingly lower IGF-1. Furthermore, in a study of 41,528 people aged between 27 and 75 with colorectal cancer, higher exercise activity directly correlated both with lower IGF-1 a lower chance of the cancer returning and a greater chance of being alive after five years. 

Education guidance and support

You cant order people to exercise unless theyre in the army. Adopting a paternalistic approach and simply telling people is not enough. If the medical community want to help their patients embark on a road of recovery which includes regular exercise, there has to be a comprehensive and well funded package of education, guidance and support. Although some individuals may possibly have exercised enthusiastically before their diagnosis they may not have the same motivation or abilities afterwards. The cancer itself, surgery, or the anticancer therapies, have resulted in physical disability, notwithstanding the commonly associated fatigue, lethargy, weight gain and reduced esteem in body image. Patient survivors may have to relearn their exercise patterns and consider a broad range of activities, particularly those which previously they may not have considered.

Education:  It is crucial that individuals truly comprehend why exercise is so beneficial, what types are suitable and where to find local resources. Magazines such as icon are an excellent way to get the message over to patients and their relatives by providing evidence-based information, free from the shackles of the burocracy endemic within hospitals. Exercise information is beginning to emerge within oncology units but this should be more routine and better integrated within accepted practice. Ideally, advice should be available from medical staff then substantiated by written and web-based information packages. A good example is www.cancernet.co.uk which provides a comprehensive number of advice sheets related to dietary, exercise and other lifestyle issues of interest to patients and their relatives (Table.2). It encourages physical activity by explaining the benefits and providing information on a diverse range of local facilities. These include walking groups, ballroom, line and salsa dance lessons, aerobics, yoga, Pilates and fitness classes, swimming and cycling clubs, gyms, sport and leisure centres, tennis and badminton courts listing times, contact numbers and locations.

Guidance and support. Experience from cardiac rehabilitation programs indicates that information, although a good foundation, needs to be re-enforced by ongoing support and feedback. To address this we have implemented the national exercise referral scheme and highlight who it can be used for cancer rehabilitation. This involved working with Primary Care Trusts, patients, local gyms, personal fitness instructors and the national bodies which govern them. As a result of this collaboration, patients can now be prescribed exercise by their oncologist and general practitioners. Initially this is restricted to patients in complete remission with bowel cancer. As you can see from the eligibility criteria listed in table.3, many of the other criteria can apply to patients who have undergone cancer treatments. For instance, breast cancer survivors who are overweight (Body mass index > 25); those with a high cholesterol, particularly relevant to men with prostate cancer; depressed or anxious patients; those who have experienced a period of inactivity; those suffering muscle or joint pains; with hypertension or diabetes following steroids or biological agents. Following a consultation with their doctor the participant presents their prescription to a designated registered exercise professional within a locally approved municipal gym. Following an initial assessments they are guided to a bespoke exercise program which is enjoyable, fulfilling and sustainable. They are required to pay a substantially reduced rate of 2.50 per session (or 1.50 if on benefits). In return the exercise professional receives additional training and the sports centre gains a potential new member! There is, however, a requirement that exercise professionals are registered with the government recognised supervising body, the Register of Exercise Professionals (REP), and have achieved at least a level 3 REP qualification. We are implementing a one day course highlight the benefits of exercise after cancer and to reassure exercise professional that their input is needed and safe. There are also current plans with the Department of Heath accreditation bodies to create a level 4 qualification. This may be useful for exercise professions helping patients with ongoing medical problems but for the vast majority who just want to provide an enjoyable exercise program for cancer survivors, this is an added and unnecessary burden of expense to their already limited income. Let us hope common sense prevails.

This exercise referral scheme is part of series of lifestyle strategies offered to patients as part of a specific exit lifestyle toolbox. The contents of this toolbox are listed in Table.4 but essentially it empowers patients and their carers to make informed lifestyle decisions based on factual and relevant information. Furthermore, it reinforces that:

Exercise should not just be a passing fad, but be incorporated into our daily lives for the rest of our lives. 
 

Table 1. Summary; What can regular exercise do?

• Prevent up to third of all cancers




• Reduce the risks of cancer treatments




• Improve the tolerability of cancer treatments




• Reduce the chance of cancer relapsing




• Empower individual and help restore confidence earlier




• Improve the chance of overall cure

 
Table 2. Summary: Tips to increase daily exercise activities.

1. Daily choices During the day we have several choices, which require more or less levels of exertion. Try to take the more active option. Walking instead of using the car or tube for short journeys. Try getting off the bus or tube one stop earlier. Use the stairs not lifts, walk on a walkway!




2. Home If you like exercising at home it is worth having a semi-formal programme to follow. There are many useful gadgets available to make it more fun (exercise bikes, trend mills, rowing machines etc). Alternatively, follow an exercise video - there are many good ones available. When watching TV try to get up and walk around for a few minutes at every break. If you like commuter games try the readily available exercise programs (e.g. Nintendo Wii)




3. Office If possible take a walk some exercise lunchtime. Try desk exercises - You may look odd but they can keep you alert especially when you getting tired or sleepy. Don’t worry about the comments - people will secretly admire your enthusiasm. Commute in training shoes, walking briskly then change at work.
   Social life There is an alternative to the pub or the TV. Exercise can and should be sociable and enjoyable - find something which is fun otherwise you will give it up very quickly.




4. Walking In addition to integrating walking in our daily duties, social walking groups are available in many areas and a good way to meet new people, view interesting scenery and exercise to a variety of ability levels.




5. Cycling Cycling socially with family or part of a daily commute even if only once or twice a week can be fun and even save money. Consider buying a bike with a basket for the shopping.




6. Gym Joining a gym is always a good start. Paying money every month is a good incentive to use it. Even if you are overweight or unfit don’t worry so are most other people and nobody of worth will criticise your efforts.




7. Exercise classes There are numerous enjoyable ways to exercise in groups one at a variety of levels. Your local sports centre will also have many activities from 5-aside football, squash, badminton, volleyball, netball as well as numerous exercise aerobics classes.




8. Swimming  Many pools offer classes to leaning to swim, single sex, or disabled.




9. Dance There are numerous dance classes available in most towns from traditional ballroom, line dancing, ballroom to Rock & Roll or Salsa.

 
Table 3. Summary of inclusion criteria for exercise referral scheme (cancer related)

Table 4. Summary: The post treatment lifestyle toolbox

Verbal: 

• - An end of treatment interview with an information nurse


• - nutritional screening questionnaire completed


• - emphasise the importance of exercise


• - describe local exercise facilities


• - encourage all the family to take part


• - explain the exercise referral scheme

Referrals:

• - to dietician is there are specific nutritional concerns


• - to a physiotherapist if there are specific disabilities which preclude exercise


• - make an exercise referral prescription if an exercise professional is required#

Written materials

• - Manual; Lifestyle after Cancer- the facts*


• - A list of local exercise facilities


• - A list of local exercise professional


• - A list of local yoga and pilates classes


• - A list of health food shops and outlets

Web bases support (cancernet.co.uk)

• - Further background information on cancer and lifestyle


• - Lifestyle news


• - A blog to interact and communicate with other lifestyle survivors


• - a portal for other lifestyle services such a specific nutritional hair and serum analysis

* The Book Lifestyle after Cancer is available from cancernet.co.uk/books.htm.
 # Eligible patients and their partners

Professor Robert Thomas FRCP MD FRCR
Cranfield University, Addenbrookes and Bedford Cambridge University NHS Trusts,
c/o The Primrose Unit, Bedford Hospital,  Bedford MK42 9DJ. 
Web: http://www.cancernet.co.uk/, E-mail [email protected]